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IntroductionIt is uncertain whether e-cigarettes facilitate smoking cessation in the real world. We aimed to understand whether and how transitions among cigarette, e-cigarette, and dual use are associated with sociodemographics, dependence measures, and biomarkers.Aims and methodsWe followed 380 adult daily cigarette users and dual users every 2 months for up to 2 years. We estimated transition rates between noncurrent, cigarette-only, e-cigarette-only, and dual use states using a multistate transition model. We estimated univariable hazard ratios (HR) for demographics, dependence measures for cigarettes and e-cigarettes, biomarkers, spousal or partner behaviors, and other measures.ResultsWe estimated that participants transitioned from cigarette-only to e-cigarette-only through a period of dual use. Dual users ceased smoking (transitioning to e-cigarette-only use) at a greater rate than cigarette-only users did (HR 2.44, 95% CI: 1.49, 4.02). However, of the 60% of dual users estimated to transition to single product use in 1 year, 83% would transition to cigarette-only use and only 17% to e-cigarette-only use. E-cigarette dependence measures were generally associated with reduced e-cigarette cessation rather than enhanced cigarette cessation. E-cigarette users motivated by harm or toxicity reduction or because of restrictions on where or when they could smoke had reduced rates of smoking relapse. Cigarette dependence and spousal smoking were barriers to cigarette cessation for dual users, while using e-cigarettes first in the morning, motivation to quit smoking, and sensory, social, and emotional enjoyment of e-cigarettes (secondary dependence motives) were facilitators of smoking cessation among dual users.ConclusionsTobacco control policy and interventions may be informed by the barriers and facilitators of product transitions.ImplicationsAlthough e-cigarettes have the potential to promote smoking cessation, their real-world impact is uncertain. In this cohort, dual users were more likely to quit smoking than cigarette-only users, but the overall impact was small because most dual users returned to cigarette-only use. Moreover, e-cigarette dependence promoted continued dual use rather than smoking cessation. Yet, high motivation to quit smoking and the sensory, social, and emotional enjoyment of e-cigarettes facilitated smoking cessation in dual users. Better understanding the barriers and facilitators of transitions can help to develop regulations and interventions that lead to more effective use of e-cigarettes for smoking cessation.

BackgroundMammography screening can lead to overdiagnosis-that is, screen-detected breast cancer that would not have caused symptoms or signs in the remaining lifetime. There is no consensus about the frequency of breast cancer overdiagnosis.ObjectiveTo estimate the rate of breast cancer overdiagnosis in contemporary mammography practice accounting for the detection of nonprogressive cancer.DesignBayesian inference of the natural history of breast cancer using individual screening and diagnosis records, allowing for nonprogressive preclinical cancer. Combination of fitted natural history model with life-table data to predict the rate of overdiagnosis among screen-detected cancer under biennial screening.SettingBreast Cancer Surveillance Consortium (BCSC) facilities.ParticipantsWomen aged 50 to 74 years at first mammography screen between 2000 and 2018.MeasurementsScreening mammograms and screen-detected or interval breast cancer.ResultsThe cohort included 35 986 women, 82 677 mammograms, and 718 breast cancer diagnoses. Among all preclinical cancer cases, 4.5% (95% uncertainty interval [UI], 0.1% to 14.8%) were estimated to be nonprogressive. In a program of biennial screening from age 50 to 74 years, 15.4% (UI, 9.4% to 26.5%) of screen-detected cancer cases were estimated to be overdiagnosed, with 6.1% (UI, 0.2% to 20.1%) due to detecting indolent preclinical cancer and 9.3% (UI, 5.5% to 13.5%) due to detecting progressive preclinical cancer in women who would have died of an unrelated cause before clinical diagnosis.LimitationsExclusion of women with first mammography screen outside BCSC.ConclusionOn the basis of an authoritative U.S. population data set, the analysis projected that among biennially screened women aged 50 to 74 years, about 1 in 7 cases of screen-detected cancer is overdiagnosed. This information clarifies the risk for breast cancer overdiagnosis in contemporary screening practice and should facilitate shared and informed decision making about mammography screening.Primary funding sourceNational Cancer Institute.

Background: The burden of diarrheal diseases remains high among children in low- income countries. Enteropathogens are challenging to control because they are transmitted via multiple pathways. Chickens are an important animal protein source, but live chickens and their products are often highly contaminated with enteropathogens. Objectives: We conducted this study to a) understand the contribution of multiple transmission pathways to the force of infection of Campylobacter spp. and nontyphoidal Salmonella spp., b) quantify the potential impact of reducing each pathway on human infection, and c) quantify hypothesized pathway reduction from the context of Maputo, Mozambique. Methods: We developed transmission models for Campylobacter and Salmonella that captured person-to-person, water- to- person, food-to-person, soil-to-person, animal-to-person, and all-other-sources-to-person in an urban, low-income setting in Mozambique. We calibrated these models using prevalence data from Maputo, Mozambique and estimates of attributable fraction of transmission pathways for the region. We simulated the prevalence of human infection after reducing transmission through each pathway. Results: Simulation results indicated that if foodborne transmission were reduced by 90%, the prevalence of Campylobacter and Salmonella infection would decline by [52.2%; 95% credible interval (CrI): 39.7, 63.8] and (46.9%; 95% CrI: 39, 55.4), respectively. Interruption of any other pathway did not have a substantial impact. Combined with survey and microbiology data, if contamination of broiler chicken meat at informal markets in Maputo could be reduced by 90%, the total infection of Campylobacter and Salmonella could be reduced by 21% (16-26%) and 12% (10- 13%), respectively. Discussion: Our transmission models showed that the foodborne transmission has to be reduced to control enteropathogen infections in our study site, and likely in other similar contexts, but mitigation of this transmission pathway has not received sufficient attention. Our model can serve as a tool to identify effective mitigation opportunities to control zoonotic enteropathogens. https://doi.org/10.1289/EHP12314, Introduction Diarrheal diseases are a substantial source of childhood morbidity and mortality. (1) In contexts where enteropathogen transmission is high, repeated asymptomatic infections also contributed to undernutrition and growth faltering [...]

Rotavirus is considered a directly transmitted disease due to its high infectivity. Environmental pathways have, therefore, largely been ignored. Rotavirus, however, persists in water sources, and both its surface water concentrations and infection incidence vary with temperature. Here, we examine the potential for waterborne rotavirus transmission. We use a mechanistic model that incorporates both direct and waterborne transmission pathways, coupled with a hydrological model, and we simulate rotavirus transmission between two communities with interconnected water sources. To parameterize temperature dependency, we estimated temperature-dependent decay rates in water through a meta-analysis. Our meta-analysis suggests that rotavirus decay rates are positively associated with temperature (n = 39, P [Formula: see text] 0.001). This association is stronger at higher temperatures (over 20 °C), consistent with tropical climate conditions. Our model analysis demonstrates that water could disseminate rotavirus between the two communities for all modeled temperatures. While direct transmission was important for disease amplification within communities, waterborne transmission could also amplify transmission. In standing-water systems, the modeled increase in decay led to decreased disease, with every 1 °C increase in temperature leading to up to a 2.4% decrease in incidence. These effect sizes are consistent with prior meta-analyses, suggesting that environmental transmission through water sources may partially explain the observed associations between temperature and rotavirus incidence. Waterborne rotavirus transmission is likely most important in cooler seasons and in communities that use slow-moving or stagnant water sources. Even when indirect transmission through water cannot sustain outbreaks, it can seed outbreaks that are maintained by high direct transmission rates.

As the appreciation for the importance of the environment in infectious disease transmission has grown, so too has interest in pathogen fate and transport. Fate has been traditionally described by simple exponential decay, but there is increasing recognition that some pathogens demonstrate a biphasic pattern of decay-fast followed by slow. While many have attributed this behavior to population heterogeneity, we demonstrate that biphasic dynamics can arise through a number of plausible mechanisms. We examine the identifiability of a general model encompassing three such mechanisms: population heterogeneity, hardening off, and the existence of viable-but-not-culturable states. Although the models are not fully identifiable from longitudinal sampling studies of pathogen concentrations, we use a differential algebra approach to determine identifiable parameter combinations. Through case studies using Cryptosporidium and Escherichia coli, we show that failure to consider biphasic pathogen dynamics can lead to substantial under- or overestimation of disease risks and pathogen concentrations, depending on the context. More reliable models for environmental hazards and human health risks are possible with an improved understanding of the conditions in which biphasic die-off is expected. Understanding the mechanisms of pathogen decay will ultimately enhance our control efforts to mitigate exposure to environmental contamination.

BACKGROUND: The burden of diarrheal diseases remains high among children in low-income countries. Enteropathogens are challenging to control because they are transmitted via multiple pathways. Chickens are an important animal protein source, but live chickens and their products are often highly contaminated with enteropathogens. OBJECTIVES: We conducted this study to a) understand the contribution of multiple transmission pathways to the force of infection of Campylobacter spp. and nontyphoidal Salmonella spp., b) quantify the potential impact of reducing each pathway on human infection, and c) quantify hypothesized pathway reduction from the context of Maputo, Mozambique. METHODS: We developed transmission models for Campylobacter and Salmonella that captured person-to-person, water-to-person, food-to-person, soil-to-person, animal-to-person, and all-other-sources-to-person in an urban, low-income setting in Mozambique. We calibrated these models using prevalence data from Maputo, Mozambique and estimates of attributable fraction of transmission pathways for the region. We simulated the prevalence of human infection after reducing transmission through each pathway. RESULTS: Simulation results indicated that if foodborne transmission were reduced by 90%, the prevalence of Campylobacter and Salmonella infection would decline by [52.2%; 95% credible interval (CrI): 39.7, 63.8] and (46.9%; 95% CrI: 39, 55.4), respectively. Interruption of any other pathway did not have a substantial impact. Combined with survey and microbiology data, if contamination of broiler chicken meat at informal markets in Maputo could be reduced by 90%, the total infection of Campylobacter and Salmonella could be reduced by 21% (16–26%) and 12% (10–13%), respectively. DISCUSSION: Our transmission models showed that the foodborne transmission has to be reduced to control enteropathogen infections in our study site, and likely in other similar contexts, but mitigation of this transmission pathway has not received sufficient attention. Our model can serve as a tool to identify effective mitigation opportunities to control zoonotic enteropathogens. https://doi.org/10.1289/EHP12314 [ABSTRACT FROM AUTHOR]

For vector-borne diseases the basic reproduction number R0 , a measure of a disease's epidemic potential, is highly temperature-dependent. Recent work characterizing these temperature dependencies has highlighted how climate change may impact geographic disease spread. We extend this prior work by examining how newly emerging diseases, like Zika, will be impacted by specific future climate change scenarios in four diverse regions of Brazil, a country that has been profoundly impacted by Zika. We estimated a R0(T) , derived from a compartmental transmission model, characterizing Zika (and, for comparison, dengue) transmission potential as a function of temperature-dependent biological parameters specific to Aedes aegypti. We obtained historical temperature data for the five-year period 2015–2019 and projections for 2045–2049 by fitting cubic spline interpolations to data from simulated atmospheric data provided by the CMIP-6 project (specifically, generated by the GFDL-ESM4 model), which provides projections under four Shared Socioeconomic Pathways (SSP). These four SSP scenarios correspond to varying levels of climate change severity. We applied this approach to four Brazilian cities (Manaus, Recife, Rio de Janeiro, and São Paulo) that represent diverse climatic regions. Our model predicts that the R0(T) for Zika peaks at 2.7 around 30°C, while for dengue it peaks at 6.8 around 31°C. We find that the epidemic potential of Zika will increase beyond current levels in Brazil in all of the climate scenarios. For Manaus, we predict that the annual R0 range will increase from 2.1–2.5, to 2.3–2.7, for Recife we project an increase from 0.4–1.9 to 0.6–2.3, for Rio de Janeiro from 0–1.9 to 0–2.3, and for São Paulo from 0–0.3 to 0–0.7. As Zika immunity wanes and temperatures increase, there will be increasing epidemic potential and longer transmission seasons, especially in regions where transmission is currently marginal. Surveillance systems should be implemented and sustained for early detection. Author summary: Rising temperatures through climate change are expected to increase arboviral disease pressure, so understanding the impact of climate change on newly emerging diseases such as Zika is essential to prepare for future outbreaks. However, because disease transmission may be less effective at very high temperatures, it is uncertain whether risk will uniformly increase in different regions. Given the nonlinear relationship between temperature and many important biological vector traits, mathematical modeling is a useful tool for predicting the impact of temperature on arbovirus risk. We used a temperature-dependent infectious disease transmission model to derive a temperature-dependent basic reproduction number. We then used historical temperature data and temperature projections for the years 2045–2049 to forecast Zika risk in four cities in Brazil under various climate change scenarios. We predict an overall increase in arbovirus risk, as well as extended risk seasons in cities that are not currently suitable for year-round spread, such as Rio de Janeiro. We also found little-to-no protective effect of increasing temperatures even in warmer climates like Manaus. Our results indicate that preparation for future Zika outbreaks (and of those of other arboviruses including dengue) should include the implementation of national disease surveillance and early detection systems. [ABSTRACT FROM AUTHOR]

Randomized controlled trials (RCTs) evaluate hypotheses in specific contexts and are often considered the gold standard of evidence for infectious disease interventions, but their results cannot immediately generalize to other contexts (e.g., different populations, interventions, or disease burdens). Mechanistic models are one approach to generalizing findings between contexts, but infectious disease transmission models (IDTMs) are not immediately suited for analyzing RCTs, since they often rely on time-series surveillance data. We developed an IDTM framework to explain relative risk outcomes of an infectious disease RCT and applied it to a water, sanitation, and hygiene (WASH) RCT. This model can generalize the RCT results to other contexts and conditions. We developed this compartmental IDTM framework to account for key WASH RCT factors: i) transmission across multiple environmental pathways, ii) multiple interventions applied individually and in combination, iii) adherence to interventions or preexisting conditions, and iv) the impact of individuals not enrolled in the study. We employed a hybrid sampling and estimation framework to obtain posterior estimates of mechanistic parameter sets consistent with empirical outcomes. We illustrated our model using WASH Benefits Bangladesh RCT data (n = 17,187). Our model reproduced reported diarrheal prevalence in this RCT. The baseline estimate of the basic reproduction number R0 for the control arm (1.10, 95% CrI: 1.07, 1.16) corresponded to an endemic prevalence of 9.5% (95% CrI: 7.4, 13.7%) in the absence of interventions or preexisting WASH conditions. No single pathway was likely able to sustain transmission: pathway-specific R0s for water, fomites, and all other pathways were 0.42 (95% CrI: 0.03, 0.97), 0.20 (95% CrI: 0.02, 0.59), and 0.48 (95% CrI: 0.02, 0.94), respectively. An IDTM approach to evaluating RCTs can complement RCT analysis by providing a rigorous framework for generating data-driven hypotheses that explain trial findings, particularly unexpected null results, opening up existing data to deeper epidemiological understanding. Author summary: A randomized controlled trial (RCT) testing an intervention to reduce infectious disease transmission can provide high-quality scientific evidence about the impact of that intervention in a specific context, but the results are often difficult to generalize to other policy-relevant contexts and conditions. Infectious disease transmission models can be used to explore what might happen to disease dynamics under different conditions, but the standard use of these models is to fit to longitudinal, surveillance data, which is rarely collected by RCTs. We developed a framework to fit an infectious disease model to steady-state diarrheal prevalence data in water, sanitation, and hygiene RCTs, explicitly accounting for completeness, coverage, compliance, and other factors. Although this framework is developed with water, sanitation, and hygiene interventions for enteropathogens in mind, it could be extended to other disease contexts. By leveraging existing large-scale RCT data sets, it will be possible to better understand the underlying disease epidemiology and investigate the likely outcomes of policy-relevant scenarios. Ultimately, this work can be incorporated into decision making for public health policy and programs. [ABSTRACT FROM AUTHOR]

Background: Understanding the impact of patient and tumor characteristics on lung cancer survival can help to build personalized prognostic models and identify health disparities.Methods: We identified 557,555 patients aged 25+ years diagnosed with lung/bronchus carcinoma from the SEER database, 2000-2016. We estimated hazard ratios (HR) for demographic (sex, age, race and ethnicity), tumor (stage, histology, year of diagnosis), and geographic characteristics (census-tract-level urbanicity, socioeconomic status (SES)), as well as selected interactions, on the rate of lung-cancer-specific death using multivariable proportional hazards models.Results: Females had a higher survival (lower hazard) of lung-cancer-specific death than males (HR 0.83, 95% CI: 0.82, 0.83). Hazards differed by race and ethnicity. Regional (HR: 2.41, 95% CI: 2.37, 2.44) and distant (HR: 6.61, 95% CI: 6.53, 6.69) tumors were associated with a lower survival (higher hazard) than localized tumors. Small-cell tumors were associated with a lower survival (HR 1.19, 95% CI: 1.18, 1.20) than non-small-cell tumors. Patients diagnosed after 2009 had lower hazards (HR 0.86, 95% CI: 085, 0.86) than those diagnosed 2000-2009. Lung-cancer-specific survival did not depend on urbanicity after adjusting for census-tract-level SES, but survival decreased with decreasing census-tract-level SES. Differences in survival between non-Hispanic Black and White patients were greater for younger patients and localized tumors and increased with census-tract-level SES. Differences by sex were greatest for young patients and localized tumors.Conclusions: Disparities in survival after lung cancer diagnosis remain, with intersectional patterns suggesting differential access to and quality of care. Efforts are needed to ensure high-risk groups receive guideline-concordant treatment. [ABSTRACT FROM AUTHOR]

Introduction: Definitions of current tobacco and nicotine delivery product use vary and depend on frequency of use, established-use criteria, and the product type. Previous research has not considered how transition rates between current use of different products depend on the current use definition.Aims and Methods: We applied a multistate transition model to data on U.S. adults from waves 1-4 (2013-2017) of the Population Assessment of Tobacco and Health (PATH) study. We estimated transition rates between never, non-current, cigarette, electronic nicotine delivery systems (ENDS), and dual use states with and without established-use criteria (has smoked 100+ cigarettes in their lifetime; ever fairly regularly used ENDS) and different frequency thresholds (1+, 10+, 20+, and 30 days of the past 30 days). We considered use below a frequency threshold as either non-current use or a distinct, infrequent use category.Results: When treating use below a frequency threshold as non-current use, transition probability estimates were largely robust to the choice of use frequency threshold, although sole ENDS users were more likely to transition to non-current use or dual use as the current use threshold increased. Removing the established-use criterion for ENDS reduced the estimates of sole ENDS and dual users staying in their use state. When treating infrequent use as a separate category, transition probability estimates were dependent on the use frequency threshold, particularly transitions among the dual use states.Conclusions: Product use definitions have important implications for assessing product use transitions and thus the public health implications of cigarette and ENDS control strategies.Implications: How we define "current use" of tobacco and nicotine delivery products changes our estimates of how individuals transition to, between, and from different patterns of use. We show that the robustness of transition estimates to whether or not non-established users are included as current users and to different frequency-of-use threshold depends in part on whether low-frequency users are categorized as non-current users or as a distinct category. Our results emphasize the importance of intentional definitions of product use that reflect the larger goals of public health and tobacco control. [ABSTRACT FROM AUTHOR]

We determined baseline oral and cervicogenital human papillomavirus (HPV) prevalence and determinants of infection in the Michigan HPV and Oropharyngeal Cancer (MHOC) study. We enrolled 394 college-age and older participants of both sexes in Ann Arbor, Michigan and the surrounding area. All participants provided an oral sample at baseline, and 130 females provided a cervicogenital sample. Samples were tested for 18 HPV genotypes using polymerase chain reaction (PCR) MassArray. Participants filled out sociodemographic and behavioral questionnaires. Prevalence ratios for HPV oral or cervicogenital prevalence by predictor variables were estimated in univariable log-binomial models. Analysis was conducted 2018–20. In the full cohort, baseline oral HPV prevalence was 10.0% for any detected genotype (among the 338 valid oral tests at baseline) and 6.5% for high-risk types, and cervicogenital prevalence was 20.0% and 10.8%, respectively (among the 130 first valid cervicogenital tests). Oral HPV prevalence did not vary by sex, with 10.5% of women and 9.0% of men having an infection. We found a high prevalence of oral and cervicogenital HPV infection in college-age participants reporting no lifetime sexual partners. Reporting a single recent partner was associated with a lower oral HPV prevalence (PR 0.39, 95% CI: 0.16, 0.96) than reporting no recent (but at least one ever) partner. No similar protective effect was seen for cervicogenital HPV. Both oral and cervicogenital prevalence increased with the number of recent partners for most sexual behaviors. We observed an ecological fallacy masking the direction of impact of vaccination on HPV prevalence in the full cohort compared to the college-aged and the age 23+ populations considered separately. Substance use was not significantly associated with oral or cervicogenital HPV infection. Many studies report substantially higher oral HPV infection prevalence in men than in women. That difference may not be uniform across populations in the US. [ABSTRACT FROM AUTHOR]

An individual's antibody titers to influenza A strains are a result of the complicated interplay between infection history, cross-reactivity, immune waning, and other factors. It has been challenging to disentangle how population-level patterns of humoral immunity change as a function of age, calendar year, and birth cohort from cross-sectional data alone. We analyzed 1,589 longitudinal sera samples from 260 children across three studies in Nicaragua, 2006–16. Hemagglutination inhibition (HAI) titers were determined against four H3N2 strains, one H1N1 strain, and two H1N1pdm strains. We assessed temporal patterns of HAI titers using an age–period–cohort modeling framework. We found that titers against a given virus depended on calendar year of serum collection and birth cohort but not on age. Titer cohort patterns were better described by participants' ages relative to year of likely introduction of the virus's antigenic cluster than by age relative to year of strain introduction or by year of birth. These cohort effects may be driven by a decreasing likelihood of early-life infection after cluster introduction and by more broadly reactive antibodies at a young age. H3N2 and H1N1 viruses had qualitatively distinct cohort patterns, with cohort patterns of titers to specific H3N2 strains reaching their peak in children born 3 years prior to that virus's antigenic cluster introduction and with titers to H1N1 and H1N1pdm strains peaking for children born 1–2 years prior to cluster introduction but not being dramatically lower for older children. Ultimately, specific patterns of strain circulation and antigenic cluster introduction may drive population-level antibody titer patterns in children. Author summary: The human antibody response to influenza A viruses is complex, in part because these viruses readily mutate to evade our immune systems. Occasional greater genetic changes can establish a new group of viruses, called an antigenic cluster, based on the similarity of our antibody responses. A better understanding of how our antibody responses change over time could improve vaccination strategies around strain selection, vaccination timing, whether yearly vaccination is optimal, and how much variability in vaccination response by age to expect. In this study, we examined how antibody responses change along three dimensions of time, namely age, calendar year, and birth cohort. As expected, antibody titers depended on what years each influenza subtype circulated. We also found that antibody responses to a virus depended on one's age when a related virus from the same antigenic cluster first circulated, not when that specific virus circulated. We also find evidence young children may have antibodies that cross-react with strains that have not yet circulated, possibly indicating that their immune systems are creating a wide array of antibodies, which could inform possible mechanisms of antigenic seniority. Our results shed new light on the dynamics of antibody titer levels. [ABSTRACT FROM AUTHOR]

Species diversity may play an important role in the modulation of pathogen transmission through the dilution effect. Infectious disease models can help elucidate mechanisms that may underlie this effect. While many modeling studies have assumed direct host-to-host transmission, many pathogens are transmitted through the environment. We present a mathematical modeling analysis exploring conditions under which we observe the dilution effect in systems with environmental transmission where host species interact through fully or partially overlapping habitats. We measure the strength of the dilution effect by the relative decrease in the basic reproduction number of two-species assemblages compared with that of a focal host species. We find that a dilution effect is most likely when the pathogen is environmentally persistent (frequency-dependent-like transmission). The magnitude of this effect is strongest when the species with the greater epidemic potential is relatively slow to pick up pathogens in the environment (density-dependent transmission) and the species with the lesser epidemic potential is efficient at picking up pathogens (frequency-dependent transmission). These findings suggest that measurable factors, including pathogen persistence and the host's relative efficiency of pathogen pickup, can guide predictions of when biodiversity might lead to a dilution effect and may thus give concrete direction to future ecological work. [ABSTRACT FROM AUTHOR]

Introduction: A better understanding of how menthol cigarette flavoring and ENDS impact smoking initiation, cessation, and transitions between tobacco products could help elucidate the potential impact of a U.S. menthol ban on combustible tobacco products.Methods: A multistate transition model was applied to data on 23,232 adults from Waves 1-4 (2013-2017) of the Population Assessment of Tobacco and Health Study (analysis was conducted in 2020-2021). Transition rates among never, noncurrent, nonmenthol versus menthol cigarette, ENDS, and dual everyday/someday use were estimated, as were transition-specific hazard ratios for age, sex, race/ethnicity, education, and income.Results: Non-Hispanic Blacks who smoked menthol discontinued smoking at a much lower rate than those who smoked nonmenthol (hazard ratio=0.43, 95% CI=0.29, 0.64), but there was no statistically significant difference in the discontinuation rates among non-Hispanic Whites (hazard ratio=0.97, 95% CI=0.80, 1.16) or Hispanics (hazard ratio=0.81, 95% CI=0.56, 1.16). Non-Hispanic Whites who smoked menthol were more likely to become dual users than those who smoked nonmenthol (hazard ratio=1.43, 95% CI=1.14, 1.80). Young adults initiated menthol smoking at a higher rate than older adults (age 18-24 years versus ≥55 years: hazard ratio=2.45, 95% CI=1.44, 4.15) but not nonmenthol smoking (hazard ratio=1.02, 95% CI=0.62, 1.69). There were differences by sex in the impact of menthol flavor on smoking initiation and discontinuation but little difference by education or income.Conclusions: Sociodemographic differences in product transitions should be accounted for when estimating the potential impact of a menthol ban. [ABSTRACT FROM AUTHOR]

Background and aims: Reports of youth e‐cigarette use often do not disaggregate by underlying smoking status. This study compared annual 2014–19 youth estimates of past 30‐day e‐cigarette use prevalence and frequency by smoking status in the United States. Design Nationally representative, cross‐sectional, school‐based survey [National Youth Tobacco Surveys (NYTS)]. General linear models accounting for complex survey design compared e‐cigarette use prevalence by smoking status by year, overall and stratified by frequency, separately for high school (HS) and middle school (MS) students. The 2019 survey was analyzed separately because of its change in survey methodology. Setting: MSs and HSs in the United States. Participants: A total of 116 704 students from 1268 schools, ages 9–19. Measurements Students self‐reported (paper 2014–18, electronic 2019) ever and past 30‐day (current) use of e‐cigarettes and cigarettes, as well as frequent use (20–30 days of month). Findings From 2014 to 2018, current e‐cigarette use prevalence increased among never, current and former smokers in HS, but only among never and current smokers in MS (each P‐value < 0.001). E‐cigarette use increases for current HS smokers were primarily among frequent e‐cigarette users. In 2018, the absolute number of HS frequent users who were never or former smokers (420 000 combined) surpassed current smokers (370 000). In 2019, current e‐cigarette use prevalence for never, former and current smokers was 17.5% [95% confidence interval (CI) = 16.0–19.0], 53.6% (95% CI = 45.2–61.9) and 85.8% (95% CI = 81.6–89.9) for HS students, respectively, and 6.8% (95% CI = 5.9–7.7), 40.8% (95% CI = 34.7–47.0) and 78.0% (95% CI = 71.9–84.2) for MS students. That year, the number of HS never (420 000) and former smokers (570 000) using e‐cigarettes frequently eclipsed that of current smokers (390 000). Conclusions: E‐cigarette use prevalence and frequency among youth vary by smoking status, with highest levels of use among current smokers. However frequent e‐cigarette use among never smokers and former smokers has increased. [ABSTRACT FROM AUTHOR]

Background Given the challenges in implementing widespread testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is increasing interest in alternative surveillance strategies. Methods We tested nasopharyngeal swabs from 1094 decedents in the Wayne County Medical Examiner's Office for SARS-CoV-2. All decedents were assessed using a coronavirus disease 2019 (COVID-19) checklist, and decedents flagged using the checklist (298) were preferentially tested. A random sample of decedents not flagged using the checklist were also tested (796). We statistically analyzed the characteristics of decedents (age, sex, race, and manner of death), differentiating between those flagged using the checklist and not and between those SARS-CoV-2–positive and not. Results A larger percentage of decedents overall were male (70% vs 48%) and black (55% vs 36%) compared with the catchment population. Seven-day average percent positivity among flagged decedents closely matched the trajectory of percent positivity in the catchment population, particularly during the peak of the outbreak (March and April 2020). After a lull in May to mid-June, new positive tests in late June coincided with increased case detection in the catchment. We found large racial disparities in test results; SARS-CoV-2–positive decedents were substantially more likely to be black than SARS-CoV-2–negative decedents (82% vs 51%). SARS-CoV-2–positive decedents were also more likely to be older and to have died of natural causes, including of COVID-19 disease. Conclusions Disease surveillance through medical examiners and coroners could supplement other forms of surveillance and serve as a possible early outbreak warning sign. [ABSTRACT FROM AUTHOR]

Background: Anatomical site is strongly associated with head and neck cancer etiology, and etiology and patient sociodemographic characteristics are prognostic factors for survival. It is not known whether the effects of these predictors persist over the postdiagnosis period or are strongest proximal to the time of diagnosis. Methods: Using survival times and causes of death for 180,434 patients with head and neck cancer in the Surveillance, Epidemiology, and End Results cancer registry (1973‐2015), the empirical cumulative incidences of cancer‐specific death and other‐cause death were calculated with a competing risks framework, and the time‐dependent effects (hazard ratios) of anatomical tumor site (oropharynx, oral cavity, or hypopharynx/larynx), age, sex, race, and year of diagnosis on cancer‐specific death and other‐cause death, stratified by tumor stage, were estimated. Results: All effects were significantly time‐varying (P <.001). Patients with nonoropharyngeal cancer had a higher hazard of cancer‐specific death but a similar cumulative fraction of deaths because of a higher rate of death from other causes. Cancer‐specific survival has not changed for patients with nonoropharyngeal cancer over the past decades but has improved since 2000 for patients with oropharyngeal cancer. The effects of age and sex on cancer survival were strongest proximal to the diagnosis, whereas the effect of race persisted over time. Conclusions: Recent improvements in survival for patients with oropharyngeal cancer may be due more to an increasing fraction of cancers attributable to human papillomavirus than to increasing treatment effectiveness. The prognostic strength of anatomical site and other predictors changes over the postdiagnosis period. Lay Summary: It is generally assumed that the effects of tumor and personal characteristics on the survival of patients with head and neck cancer are fixed over time, but this study shows that many factors are most important only in the first few years after diagnosis.Also, recent improvements in the survival of patients with head and neck cancer appear to benefit only patients with cancers of the oropharynx. The improvements may be due more to an increasing fraction of cancers caused by human papillomavirus (which generally have better outcomes) than to advances in head and neck cancer treatment overall. The prognostic strength of tumor and patient characteristics for predicting patient survival changes over the postdiagnosis period. Recent improvements in survival for patients with oropharyngeal cancer may be due more to an increasing fraction of cancers attributable to human papillomavirus than to increasing treatment effectiveness. [ABSTRACT FROM AUTHOR]

Introduction Human papillomavirus (HPV) is the primary cause of cervical and other anogenital cancers and is also associated with head and neck cancers. Incidence of HPV-related oropharyngeal squamous cell cancers (OPSCCs) is increasing, and HPV-related OPSCCs have surpassed cervical cancer as the most common HPVrelated cancer in the USA. Given the multisite nature of HPV, there is strong interest in collecting data from both genital and oral sites, as well as associated data on social and sexual behaviours. The overarching goal of this study is to evaluate patterns of oral HPV infection incidence, clearance and persistence and their relationship to sexual behaviour history. Methods and analysis Participants are recruited from two populations: college students at a large public university and general population from the surrounding area. At the first study visit, participants complete a detailed sexual history, health and behaviour questionnaire. Follow-up visits occur every 3-4 months over 3 years, when participants complete an abbreviated questionnaire. All participants provide a saliva sample at each visit, and eligible participants may provide a cervicovaginal selfswab. Genetic material isolated from specimens is tested for 15 high-risk and 3 low-risk HPV types. Statistical analyses will examine outcome variables including HPV prevalence, incidence, persistence and clearance. Logistic regression models will be used to estimate odds ratios and 95% confidence intervals for associations between the outcomes of interest and demographic/behavioural variables collected in the questionnaires. The longitudinal HPV infection data and detailed sexual history data collected in the questionnaires will allow us to develop individual-based network models of HPV transmission and will be used to parameterise multiscale models of HPVrelated OPSC carcinogenesis. Ethics and dissemination This study has been approved by the University of Michigan Institutional Review Board. All participants are consented in person by trained study staff. Study results will be disseminated through peer-reviewed publications. [ABSTRACT FROM AUTHOR]

A correction to the article "Parameter Estimation for Multistage Clonal Expansion Models From Cancer Incidence Data: A Practical Identifiability Analysis," that was published in a 2017 issue of "PLOS Computational Biology" is presented.

Multistage clonal expansion (MSCE) models of carcinogenesis are continuous-time Markov process models often used to relate cancer incidence to biological mechanism. Identifiability analysis determines what model parameter combinations can, theoretically, be estimated from given data. We use a systematic approach, based on differential algebra methods traditionally used for deterministic ordinary differential equation (ODE) models, to determine identifiable combinations for a generalized subclass of MSCE models with any number of preinitation stages and one clonal expansion. Additionally, we determine the identifiable combinations of the generalized MSCE model with up to four clonal expansion stages, and conjecture the results for any number of clonal expansion stages. The results improve upon previous work in a number of ways and provide a framework to find the identifiable combinations for further variations on the MSCE models. Finally, our approach, which takes advantage of the Kolmogorov backward equations for the probability generating functions of the Markov process, demonstrates that identifiability methods used in engineering and mathematics for systems of ODEs can be applied to continuous-time Markov processes. [ABSTRACT FROM AUTHOR]

Environmentally mediated infectious disease transmission models provide a mechanistic approach to examining environmental interventions for outbreaks, such as water treatment or surface decontamination. The shift from the classical SIR framework to one incorporating the environment requires codifying the relationship between exposure to environmental pathogens and infection, i.e. the dose–response relationship. Much of the work characterizing the functional forms of dose–response relationships has used statistical fit to experimental data. However, there has been little research examining the consequences of the choice of functional form in the context of transmission dynamics. To this end, we identify four properties of dose–response functions that should be considered when selecting a functional form: low-dose linearity, scalability, concavity, and whether it is a single-hit model. We find that i) middle- and high-dose data do not constrain the low-dose response, and different dose–response forms that are equally plausible given the data can lead to significant differences in simulated outbreak dynamics; ii) the choice of how to aggregate continuous exposure into discrete doses can impact the modeled force of infection; iii) low-dose linear, concave functions allow the basic reproduction number to control global dynamics; and iv) identifiability analysis offers a way to manage multiple sources of uncertainty and leverage environmental monitoring to make inference about infectivity. By applying an environmentally mediated infectious disease model to the 1993 Milwaukee Cryptosporidium outbreak, we demonstrate that environmental monitoring allows for inference regarding the infectivity of the pathogen and thus improves our ability to identify outbreak characteristics such as pathogen strain. [ABSTRACT FROM AUTHOR]

Many cancers are understood to be the product of multiple somatic mutations or other rate-limiting events. Multistage clonal expansion (MSCE) models are a class of continuous-time Markov chain models that capture the multi-hit initiation–promotion–malignant-conversion hypothesis of carcinogenesis. These models have been used broadly to investigate the epidemiology of many cancers, assess the impact of carcinogen exposures on cancer risk, and evaluate the potential impact of cancer prevention and control strategies on cancer rates. Structural identifiability (the analysis of the maximum parametric information available for a model given perfectly measured data) of certain MSCE models has been previously investigated. However, structural identifiability is a theoretical property and does not address the limitations of real data. In this study, we use pancreatic cancer as a case study to examine the practical identifiability of the two-, three-, and four-stage clonal expansion models given age-specific cancer incidence data using a numerical profile-likelihood approach. We demonstrate that, in the case of the three- and four-stage models, several parameters that are theoretically structurally identifiable, are, in practice, unidentifiable. This result means that key parameters such as the intermediate cell mutation rates are not individually identifiable from the data and that estimation of those parameters, even if structurally identifiable, will not be stable. We also show that products of these practically unidentifiable parameters are practically identifiable, and, based on this, we propose new reparameterizations of the model hazards that resolve the parameter estimation problems. Our results highlight the importance of identifiability to the interpretation of model parameter estimates. [ABSTRACT FROM AUTHOR]

The role of human papillomavirus (HPV) as a causative agent for epithelial cancers is well-known, but many open questions remain regarding the downstream gene regulatory effects of viral proteins E6 and E7 on the cell cycle. Here, we extend a cell cycle model originally presented by Gérard and Goldbeter (2009) in order to capture the effects of E6 and E7 on key actors in the cell cycle. Results suggest that E6 is sufficient to reverse p53-induced quiescence, while E7 is sufficient to reverse p16INK4a-induced quiescence; both E6 and E7 are necessary when p53 and p16INK4a are both active. Moreover, E7 appears to play a role as a "growth factor substitute", inducing cell division in the absence of growth factor. Low levels of E7 may permit regular cell division, but the results suggest that higher levels of E7 dysregulate the cell cycle in ways that may destabilize the cellular genome. The mechanisms explored here provide opportunities for developing new treatment targets that take advantage of the cell cycle regulatory system to prevent HPV-related cancer effects. • We developed a model of the effects of HPV on key actors in the cell cycle. • Model results suggest that E6 is sufficient to reverse p53-induced quiescence. • Simulations show E7 is sufficient to reverse p16-INK4a-induced quiescence. • We also show that both E6 and E7 are necessary when p53 and p16-INK4a are both active. • E7 may act as a growth factor substitute, inducing cell division sans growth factor. [ABSTRACT FROM AUTHOR]

Differences in prognosis in HPV-positive and HPV-negative oral (oropharyngeal and oral cavity) squamous cell carcinomas (OSCCs) and increasing incidence of HPV-related cancers have spurred interest in demographic and temporal trends in OSCC incidence. We leverage multistage clonal expansion (MSCE) models coupled with age—period—cohort (APC) epidemiological models to analyze OSCC data in the SEER cancer registry (1973–2012). MSCE models are based on the initiation—promotion—malignant conversion paradigm in carcinogenesis and allow for interpretation of trends in terms of biological mechanisms. APC models seek to differentiate between the temporal effects of age, period, and birth cohort on cancer risk. Previous studies have looked at the effect of period and cohort on tumor initiation, and we extend this to compare model fits of period and cohort effects on each of tumor initiation, promotion, and malignant conversion rates. HPV-related, HPV-unrelated except oral tongue, and HPV-unrelated oral tongue sites are best described by placing period and cohort effects on the initiation rate. HPV-related and non-oral-tongue HPV-unrelated cancers have similar promotion rates, suggesting similar tumorigenesis dynamics once initiated. Estimates of promotion rates at oral tongue sites are lower, corresponding to a longer sojourn time; this finding is consistent with the hypothesis of an etiology distinct from HPV or alcohol and tobacco use. Finally, for the three subsite groups, men have higher initiation rates than women of the same race, and black people have higher promotion than white people of the same sex. These differences explain part of the racial and sex differences in OSCC incidence. [ABSTRACT FROM AUTHOR]

Background: HPV infects multiple sites in the epithelium, including the genitals and oral cavity. The relation between genital and oral infections and serum antibodies can help explain the natural history and epidemiology of HPV.Methods: We analyzed HPV data from NHANES derived from self-collected vaginal swabs (women ages 14-59, 2003-12), oral rinses (men and women 14-69, 2009-12), and serum (men and women 14-59, 2003-10).Results: Type-concordance of cervicogenital and oral infections in women was found to vary widely by age. Prevalence of oral infections with type-concordant antibodies was low but varied by sex: 0.2 % (95 % CI 0.0-0.8) for women vs 0.8 % (95 % CI 0.4-1.3) for men. Vaccination was associated with a reduced risk of cervicogenital infection for vaccine genotypes among ages 14-17 (0.2 (95 % CI 0.1-0.8)) and 18-24 (0.2 (95 % CI 0.1-0.3). Seroprevalence trends in women showed a dramatic increase for recent birth cohorts, likely due to vaccination. By contrast, trends for men remained relatively constant. Age-specific cervicogenital prevalence showed a consistent peak in the late teens and twenties. Relative cervicogenital prevalence has largely been decreasing since the 1940-50 birth cohort.Conclusions: There are complex patterns in HPV prevalence trends and type-concordance across infection sites and serum antibodies. A multisite sampling scheme is needed to better understand the epidemiology and natural history of HPV. [ABSTRACT FROM AUTHOR]

• We estimate vaccination impact in the 2017/19 hepatitis A virus outbreak in Louisville. • Critical vaccination threshold among persons who experience homelessness or who use drugs was 77% assuming 90% vaccine efficacy. • Vaccination during the outbreak accounted for at least US$490000 in cost savings. • Earlier and faster vaccination would have led to greater impact. Between September 2017 and June 2019, an outbreak of hepatitis A virus (HAV) occurred in Louisville, Kentucky, resulting in 501 cases and 6 deaths, predominantly among persons who experience homelessness or who use drugs (PEH/PWUD). The critical vaccination threshold (V c) required to achieve herd immunity in this population is unknown. We investigated V c and vaccination impact using epidemic modeling. To determine which population subgroups had high infection risks, we employed a technique based on comparing the proportion of cases arising before and after the epidemic peak, across subgroups. We also developed a dynamic deterministic model of HAV transmission among PEH/PWUD to estimate the basic reproduction number (R 0), herd immunity threshold, V c and the effect of timing of the vaccination intervention on epidemic and economic outcomes. Of the 501 confirmed or probable cases, 385 (76.8%) were among PEH/PWUD. Among PEH/PWUD and within the general population, homelessness was a significant risk factor for infection in the initial stages of the outbreak (odds ratios for homeless versus not homeless: 2.62; 95% confidence interval (CI): 1.62–4.25 for PEH/PWUD and 2.39; 95% CI: 1.51–3.78 for all detected cases). Our estimate for R 0 ranges between 2.85 and 3.54, corresponding to an estimate of 69% (95% CI: 65–72) for herd immunity threshold and 76% (95% CI: 72%-80%) for V c , assuming a vaccine with 90% efficacy. The observed vaccination program was estimated to have averted 30 hospitalizations (95% CI: 19–43), associated with over US$490 000 (95% CI: $310 000–700 000) in hospitalization cost. Greater impact was observed with earlier and faster vaccination implementation. Vaccination coverage of at least 77% is likely required to prevent outbreaks of HAV among PEH/PWUD in Louisville, assuming a 90% vaccine efficacy. Proactive hepatitis A vaccination programs among PEH/PWUD will maximize health and economic benefits of these programs and reduce the likelihood of another outbreak. [ABSTRACT FROM AUTHOR]

The 13 C-sucrose breath test ( 13 C-SBT) has been proposed to estimate sucrase-isomaltase (SIM) activity and is a promising test for SIM deficiency, which can cause gastrointestinal symptoms, and for intestinal mucosal damage caused by gut dysfunction or chemotherapy. We previously showed how various summary measures of the 13 C-SBT breath curve reflect SIM inhibition. However, it is uncertain how the performance of these classifiers is affected by test duration. We leveraged 13 C-SBT data from a cross-over study in 16 adults who received 0, 100, and 750 mg of Reducose, an SIM inhibitor. We evaluated the performance of a pharmacokinetic-model-based classifier,ρ, and three empirical classifiers (cumulative percent dose recovered at 90 min (cPDR90), time to 50% dose recovered, and time to peak dose recovery rate), as a function of test duration using receiver operating characteristic (ROC) curves. We also assessed the sensitivity, specificity, and accuracy of consensus classifiers. Test durations of less than 2 h generally failed to accurately predict later breath curve dynamics. The cPDR90 classifier had the highest ROC area-under-the-curve and, by design, was robust to shorter test durations. For detecting mild SIM inhibition,ρhad a higher sensitivity. We recommend 13 C-SBT tests run for at least a 2 h duration. Although cPDR90 was the classifier with highest accuracy and robustness to test duration in this application, concerns remain about its sensitivity to misspecification of the CO 2 production rate. More research is needed to assess these classifiers in target populations., (Creative Commons Attribution license.)

Introduction: The use of cigarettes and electronic nicotine delivery system (ENDS) has likely changed since 2019 with the rise of pods and disposables, the lung injuries outbreak, flavour bans, Tobacco 21 and the COVID-19 pandemic., Methods: Using the Population Assessment of Tobacco and Health Study, we applied a multistate transition model to 28 061 adults in waves 4-5 (2017-2019) and 24 584 adults in waves 5-6 (2019-2021), estimating transition rates for initiation, cessation and switching products for each period overall and by age group., Results: Cigarette initiation among adults who never used either product decreased from 2017-2019 to 2019-2021, but ENDS initiation did not significantly change. The persistence of ENDS-only use remained high (75%-80% after 1 year). Cigarette-only use transitions remained similar (88% remaining, 7% to non-current use and 5% to dual or ENDS-only use). In contrast, dual use to ENDS-only transitions increased from 9.5% (95% CI 7.3% to 11.7%) to 20.0% (95% CI 17.4% to 22.6%) per year, decreasing the persistence of dual use. The dual to cigarette-only use transition remained at about 25%. These changes were qualitatively similar across adult age groups, though adults ages 18-24 years exhibited the highest probability of switching from cigarette-only use to dual use and from dual use to ENDS-only use., Conclusions: The persistence of ENDS use among adults remained high in 2019-2021, but a larger fraction of dual users transitioned to ENDS-only use compared with 2017-2019. Because the fraction of cigarette-only users switching to dual use remained low, especially among older adults, the public health implications of this change are minimal., Competing Interests: Competing interests: DTL has presented virtually at the tobacco-industry-sponsored Global Tobacco and Nicotine Forum conference but received no funds for his participation. All other authors declare that they have no conflicts of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The human papillomavirus (HPV) causes cervicovaginal, oral, and anogenital cancer, and cervical cancer screening options include HPV testing of a clinician-collected sample. Transgender and gender diverse (TGD) people assigned female at birth (AFAB) face many barriers to preventive care, including cancer screening. Self-sampling options may increase access and participation in HPV testing and cancer screening. This study estimated the prevalence of HPV in self-collected cervicovaginal, oral, and anal samples from Midwestern TGD individuals AFAB. Methods: We recruited TGD individuals AFAB for an observational study, mailing them materials to self-collect cervicovaginal, oral, and anal samples at home. We tested samples for high-risk (HR; 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) and other HPV genotypes (6, 11, 66, 68, 73, 90) using a polymerase chain reaction mass array test. Prevalence ratios for HPV infection at each site as a function of participant characteristics were estimated in log-binomial models. Results: Out of 137 consenting participants, 102 completed sample collection. Among those with valid tests, 8.8% (HR = 6.6%; HPV 16/18 = 3.3%) were positive for oral HPV, 30.5% (HR = 26.8%; HPV 16/18 = 9.7%) for cervicovaginal HPV, and 39.6% (HR = 33.3%; HPV 16/18 = 8.3%) for anal HPV. A larger fraction of oral (71.4%) than anal infections (50.0%) were concordant with a cervicovaginal infection of the same type. Conclusions: We detected HR cervicovaginal, oral, and anal HPV in TGD people AFAB. It is essential that we reduce barriers to cancer screening for TGD populations, such as through the development of a clinically approved self-screening HPV test.

Purpose: Transgender and gender diverse (TGD) people assigned female at birth (AFAB) face numerous barriers to preventive care, including for cervical cancer screening. At-home human papillomavirus (HPV) testing may expand access to cervical cancer screening for TGD people AFAB. This study assessed the perceptions of TGD individuals AFAB who self-collected cervicovaginal and anal samples. Methods: We recruited TGD individuals AFAB to collect cervicovaginal and anal specimens at home using self-sampling for HPV testing, and individuals reported their perceptions of self-sampling. Associations between demographic and health characteristics and each of comfort of use, ease of use, and willingness to use self-sampling were estimated using robust Poisson regression. Results: Of 137 consenting participants, 101 completed the sample collection and the surveys. The majority of participants reported that the cervicovaginal self-swab was not uncomfortable (68.3%) and not difficult to use (86.1%), and nearly all (96.0%) were willing to use the swab in the future. Fewer participants found the anal swab to not be uncomfortable (47.5%), but most participants still found the anal swab to not be difficult to use (70.2%) and were willing to use the swab in the future (89.1%). Participants were more willing to use either swab if they had not seen a medical professional in the past year. Conclusions: TGD individuals AFAB were willing to use and preferred self-sampling methods for cervicovaginal and anal HPV testing. Developing clinically approved self-sampling options for HPV testing could expand access to cancer screening for TGD populations.